Alternative splicing of amino-terminal tau mRNA in rat spinal cord during development and following axonal injury

Tau is a family of microtubule-associated phosphoproteins in which isoform variation is produced by alternative splicing of a single gene and posttran slational modifications, Tau isoforms that include exon 10 are overexpresse d in frontotemporal dementia and progressive supranuclear palsy. Therefore, we examined the expression of tau mRNA splice variants during axonal regen eration and abortive regeneration. Previous work in our laboratory demonstr ated that expression of exon 10 tau isoforms during regeneration and aborti ve regeneration was altered and partially recapitulated the developmental p atterns of tau isoform expression. Using RT-PCR, we examined the alternativ e splicing of exons 2 and 3 in tau during early postnatal development and r egeneration in the rat spinal cord. The levels of tau lacking exons 2 and 3 were high on the day of birth and rapidly declined, Conversely, tau isofor ms containing exon 2 or exons 2 and 3 first appeared at low levels and stea dily increased. During axonal regeneration, the levels of all three tau mRN A isoforms were significantly lower 7 days after injury, In a model of abor tive regeneration, all of the tau isoforms were elevated 14 and 42 days pos tinjury. The relative levels of exon 2 and 3 tau splice variants were not a ltered during regeneration or abortive regeneration as occurred during deve lopment. These results suggest that tau isoform expression following neuron al injury does not recapitulate the developmental pattern and is not indepe ndently regulated as in development. Our previous results together with the se data suggest that alterations in tau mRNA isoform expression that occur in neurodegeneration are not secondary to axonal injury but may be a more p rimary event underlying cytoskeletal derangement. (C) 2001 Academic Press.